Carbon-11 labeled σ₂ receptor ligands for imaging breast cancer

Four conformationally flexible benzamide analogs having a high affinity and outstanding selectivity for σ₂ versus σ₁ receptors were synthesized and radiolabeled with carbon-11 by reaction with [¹¹C]methyl iodide. The four ¹¹C-labeled radiotracers were evaluated for their potential to image the proliferative status of breast tumors with positron emission tomography (PET). In vivo studies in female BALB/C mice bearing EMT-6 breast tumors showed that one radiotracer, (2-methoxy- ¹¹C)-N-(4-(3,4-dihydro-6,7-dimethoxy-isoquinolin-2(1H)-yl)butyl) -5-methylbenzamide ([¹¹C]2), had a high tumor uptake and suitable tumor/background ratio for imaging purposes. Blocking studies were consistent with the labeling of σ₂ receptors in vivo. A study comparing the in vivo properties of [¹¹C]2 and ¹⁸F-3′-fluoro- 3′-deoxy-l-thymidine ([¹⁸F]FLT) indicated that [ ¹¹C]2 had either similar (lung, fat) or better (blood, muscle) tumor/organ ratios than [¹⁸F]FLT in the tissues that are important for breast tumor imaging. Consequently, [¹¹C]2 is a potential radiotracer for imaging the proliferative status of breast tumors in vivo with PET.